Although many studies have focused on antitumoral properties of capsaicin and alpha lipoic acid, molecular mechanisms by which selectively effects are incompletely determined. In current study, we investigated cytotoxic and apoptotic role of natural compounds on colon adenocarcinoma cells. Capcaicin was evaluated for different concentrations at Caco-2. Cytotoxic effects of capsaicin and alpha lipoic acid on Caco-2 cells were determined by MTT. However, antioxidant activities of alpha lipoic acid were evaluated when used with capsaicin or separately groups. Caspase activities were measured by apoptotic assays. Capsaicin and ALA, alone or in combination, inhibited cell growth and promoted apoptosis. Capsaicin has significant cytotoxic and apoptotic effects at 150, 300µM concentrations while alpha lipoic acid has proliferative effects with more than 400 µM on Caco-2 cells. However, we observed these compounds activate caspase 8 using the mitochondrial and death receptor pathways to induce apoptosis. Further studies at molecular level are required to support our findings and to elucidate chemotherapeutic flavonoids on colon cancer. Extrinsic, intrinsic, and mitochondrial pathway procedures show how to use apoptotic mechanism considering by stimulation. According to our results, medical plants should be used with the correct concentration and duration of the cancer type and the stage.